Urinary congophilia in women with hypertensive disorders of pregnancy and pre-existing proteinuria or hypertension

Background Congophilia indicates the presence of amyloid protein, an aggregate of misfolded proteins, implicated in the pathophysiology of preeclampsia. Recently urinary congophilia has been proposed as a test for diagnosis and prediction of preeclampsia. Objectives To determine whether urine congophilia is present in a cohort of women with preeclampsia and in pregnant and non- pregnant women with renal disease. Study design Using a Preeclampsia, Chronic Hypertension, renal disease and Systemic lupus erythematosus cohort, urine samples were analysed from healthy pregnant controls (n=31), pregnant women with preeclampsia (n=23), gestational hypertension (n=10), chronic hypertension (n=14), chronic kidney disease; n=28), chronic kidney disease with superimposed preeclampsia (n=5) and those with chronic hypertension and superimposed preeclampsia (n=12). Samples from non-pregnant controls (n=10) and non-pregnant women with either systemic lupus erythematosus with (n=25) and without lupus nephritis (n=14) were analysed. For each sample, protein concentration was standardised before mixing with Congo Red, spotting to nitrocellulose membrane and rinsing with methanol. The optical density of the residual Congo Red stain was determined, Congo red retention calculated and groups compared with Mann-Whitney test or Kruskal-Wallis Analysis of Variance test as appropriate. Results Congophilia was increased in urine from women with preeclampsia (median Congo red retention 47% [interquartile range 22-68]) compared to healthy pregnant controls (Congo red retention 16% [13-21]; p=0.002), women with gestational hypertension (Congo red retention 20% [13-27]; p=0.008) or to women with chronic hypertension (Congo red retention 17% [12-28]; p=0.01). There were no differences in Congo red retention between pregnant women with chronic hypertension and normal pregnant controls (Congo red retention 17% [12-28] vs. 16 [13-21] respectively; p=0.72). Congophilia was present in pregnant women with chronic kidney disease (Congo red retention 32% [14-57]), being similar to values found in women with preeclampsia (p=0.22) and for women with chronic kidney disease and superimposed preeclampsia (Congo red retention 57% [29-71]; p=0.18). Non-pregnant women with lupus nephritis had higher congophilia compared with non-pregnant female controls (Congo red retention 38 [17-73] vs. 9; [7-11%]; p<0.001) and non-pregnant women with systemic lupus erythematosus without nephritis (CRR 38 [17-73] vs. 13 [11-17%]; p=0.001). A significant positive correlation was observed between congophilia and protein:creatinine ratio (Spearman rank correlations 0.702; 95% confidence interval: 0.618 to 0.770; p<0.001). Conclusion This study confirms that women with preeclampsia and chronic kidney disease without preeclampsia have elevated urine congophilia compared to healthy pregnant women. Non-pregnant women with lupus nephritis also have elevated urine congophilia compared with healthy controls. An elevated Congo Red retention may not be able to differentiate between these conditions and further research is required to explore the use of congophilia in clinical practice.